BACKGROUND. The effect of adding progestins
to estrogen therapy on the risk of breast cancer in postmenopausal women is controversial.

METHODS. To quantify the relation between the use
of hormones and the risk of breast cancer in postmenopausal women, we extended our follow-up of the participants
in the Nurses Health Study to 1992. The women were asked to complete questionnaires every two years to update information
on their menopausal status, use of estrogen and progestin preparations, and any diagnosis of breast cancer. During
725,550 person-years of follow-up, we documented 1935 cases of newly diagnosed invasive breast cancer. RESULTS.
The risk of breast cancer was significantly increased among women who were currently using estrogen alone (relative
risk, 1.32; 95 percent confidence interval, 1.14 to 1.54) or estrogen plus progestin (relative risk, 1.41; 95 percent
confidence interval, 1.15 to 1.74), as compared with postmenopausal women who had never used hormones. Women currently
taking hormones who had used such therapy for 5 to 9 years had an adjusted relative risk of breast cancer of 1.46
(95 percent confidence interval, 1.22 to 1.74), as did those currently using hormones who had done so for a total
of 10 or more years (relative risk, 1.46; 95 percent confidence interval, 1.20 to 1.76). The increased risk of
breast cancer associated with five or more years of postmenopausal hormone therapy was greater among older women
(relative risk for women 60 to 64 years old, 1.71; 95 percent confidence interval, 1.34 to 2.18). The relative
risk of death due to breast cancer was 1.45 (95 percent confidence interval, 1.01 to 2.09) among women who had
taken estrogen for five or more years.

CONCLUSIONS. The addition of progestins to estrogen
therapy does not reduce the risk of breast cancer among postmenopausal women. The substantial increase in the risk
of breast cancer among older women who take hormones suggests that the trade-offs between risks and benefits should
be carefully assessed.